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Q99717 (SMAD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mothers against decapentaplegic homolog 5

Short name=MAD homolog 5
Short name=Mothers against DPP homolog 5
Alternative name(s):
JV5-1
SMAD family member 5
Short name=SMAD 5
Short name=Smad5
Short name=hSmad5
Gene names
Name:SMAD5
Synonyms:MADH5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).

Subunit structure

May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1. Ref.12 Ref.13

Subcellular location

Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.

Tissue specificity

Ubiquitous.

Post-translational modification

Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.

Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.

Sequence similarities

Belongs to the dwarfin/SMAD family.

Contains 1 MH1 (MAD homology 1) domain.

Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

Mullerian duct regression

Inferred from electronic annotation. Source: Ensembl

bone development

Inferred from electronic annotation. Source: Ensembl

cardiac muscle contraction

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from electronic annotation. Source: Ensembl

cellular response to BMP stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

embryonic pattern specification

Inferred from sequence or structural similarity. Source: UniProtKB

erythrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

germ cell development

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Non-traceable author statement Ref.1. Source: GOC

osteoblast fate commitment

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Non-traceable author statement Ref.11. Source: UniProtKB

protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.8. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Non-traceable author statement Ref.10. Source: UniProtKB

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

integral component of membrane

Non-traceable author statement Ref.11. Source: UniProtKB

intracellular

Non-traceable author statement Ref.8. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Non-traceable author statement Ref.8. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 23610558. Source: MGI

transcription factor complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionRNA polymerase II core promoter sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

receptor signaling protein activity

Non-traceable author statement Ref.1. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity

Traceable author statement PubMed 19018011. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 11278251. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 465464Mothers against decapentaplegic homolog 5
PRO_0000090865

Regions

Domain13 – 137125MH1
Domain271 – 465195MH2
Compositional bias40 – 467Poly-Lys

Sites

Metal binding651Zinc By similarity
Metal binding1101Zinc By similarity
Metal binding1221Zinc By similarity
Metal binding1271Zinc By similarity

Amino acid modifications

Modified residue21N-acetylthreonine Ref.7 Ref.19
Modified residue4631Phosphoserine Ref.17
Modified residue4651Phosphoserine Ref.17

Experimental info

Mutagenesis4191G → S: Loss of phosphorylation. Ref.5
Sequence conflict1751D → H in AAC50791. Ref.1
Sequence conflict2371N → P in AAC50791. Ref.1
Sequence conflict2931S → R in AAC50791. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q99717 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 4A1FD7EC7BD06728

FASTA46552,258
        10         20         30         40         50         60 
MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG 

        70         80         90        100        110        120 
QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE 

       130        140        150        160        170        180 
VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP 

       190        200        210        220        230        240 
NNTPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP 

       250        260        270        280        290        300 
MDTSNNMIPQ IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 

       310        320        330        340        350        360 
DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC 

       370        380        390        400        410        420 
NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW 

       430        440        450        460 
GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS 

« Hide

References

« Hide 'large scale' references
[1]"Mad-related genes in the human."
Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B.V.
Nat. Genet. 13:347-349(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor."
Hejlik D.P., Kottickal L.V., Liang H., Fairman J., Davis T., Janecki T., Sexton D., Perry W. III, Tavtigian S.V., Teng D.H., Nagarajan L.
Cancer Res. 57:3779-3783(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60."
Zavadil J., Brezinova J., Svoboda P., Zemanova Z., Michalova K.
Leukemia 11:1187-1192(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors."
Gemma A., Hagiwara K., Vincent F., Ke Y., Hancock A.R., Nagashima M., Bennett W.P., Harris C.C.
Oncogene 16:951-956(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12."
Nishimura R., Kato Y., Chen D., Harris S.E., Mundy G.R., Yoneda T.
J. Biol. Chem. 273:1872-1879(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLY-419.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[7]Bienvenut W.V., Lempens A., Norman J.C.
Submitted (OCT-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-16; 34-40; 130-158; 283-306 AND 309-319, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[8]"TGF-beta signal transduction."
Massague J.
Annu. Rev. Biochem. 67:753-791(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
Verschueren K., Huylebroeck D.
Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"The Smad pathway."
Wrana J.L., Attisano L.
Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"TGF-beta signaling by Smad proteins."
Miyazono K.
Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[12]"Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression."
Frontelo P., Leader J.E., Yoo N., Potocki A.C., Crawford M., Kulik M., Lechleider R.J.
Oncogene 23:5242-5251(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUV39H1 AND SUV39H2.
[13]"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines."
Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K.
J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LEMD3.
[14]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-465, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U59913 mRNA. Translation: AAC50791.1.
AF010601 mRNA. Translation: AAB66353.1.
AF010607 expand/collapse EMBL AC list , AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA. Translation: AAB92396.1.
U73825 mRNA. Translation: AAB95090.1.
AF009744 expand/collapse EMBL AC list , AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA. Translation: AAB82655.1.
AF009678 mRNA. Translation: AAB72180.1.
BC009682 mRNA. Translation: AAH09682.1.
RefSeqNP_001001419.1. NM_001001419.1.
NP_001001420.1. NM_001001420.1.
NP_005894.3. NM_005903.5.
UniGeneHs.167700.

3D structure databases

ProteinModelPortalQ99717.
SMRQ99717. Positions 10-133, 270-453.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110265. 56 interactions.
DIPDIP-57571N.
IntActQ99717. 28 interactions.
MINTMINT-1180224.
STRING9606.ENSP00000384803.

PTM databases

PhosphoSiteQ99717.

Polymorphism databases

DMDM13959566.

Proteomic databases

PaxDbQ99717.
PRIDEQ99717.

Protocols and materials databases

DNASU4090.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID4090.
KEGGhsa:4090.
UCSCuc003lbj.1. human.

Organism-specific databases

CTD4090.
GeneCardsGC05P135496.
HGNCHGNC:6771. SMAD5.
HPAHPA058931.
MIM603110. gene.
neXtProtNX_Q99717.
PharmGKBPA30528.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG330956.
HOVERGENHBG053353.
InParanoidQ99717.
KOK16790.
PhylomeDBQ99717.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ99717.

Gene expression databases

ArrayExpressQ99717.
BgeeQ99717.
CleanExHS_SMAD5.
GenevestigatorQ99717.

Family and domain databases

Gene3D2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERPTHR13703. PTHR13703. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMothers_against_decapentaplegic_homolog_5.
GenomeRNAi4090.
NextBio16034.
PROQ99717.
SOURCESearch...

Entry information

Entry nameSMAD5_HUMAN
AccessionPrimary (citable) accession number: Q99717
Secondary accession number(s): O14688, Q15798, Q9UQA1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM